Presenter : Ravi Bhardwaj Moderator: Anupam SibalPanelists : BR Thapa, Harshad Devarbhavi, RK Dhiman, Srinivas Sankaranarayanan

Case Discussion Acute liver failure with hemolysis – needing a transplant

Dr Ravi BharadwajFNB Pediatric Gastroenterology

Apollo Center For Advanced PediatricsIndraprastha Apollo Hospital

Presenting complaints10 year old FemalePresented in June 2016 with c/o:

Poor appetite with nauseaFatigabilityProgressive abdominal distension

Symptoms for 4 weeksTook medicines from nearby practitioner

5th week of illness Two episode of cola colored urine

painlessA day later parents noticed yellowish discoloration

of eyesDecreased urine output

No documented feverNo diarrhea/abdominal pain/vomitingNo skin lesions/joint pain/joint swelling/chest painNo dysuria/edema/pustulesNo significant drug historyNo bleeding from any site (skin, GI)No seizures/alteration in sensorium/abnormal

movements/behavioural changes

Question?

Differential diagnosis?

Past History

No history of blood transfusionNo similar history in past No history of prior admission for any illness

Developmentally normalVaccinated for ageFamily history

One younger male sibling – 7 years, wellno history of similar illness in familyNo h/o consanguinity

Dietary history: Calories 90 Cal/kg/day Protein 1.5 g/kg/day

Admitted in nearby hospitalEvaluated and referred for further evaluation

On examination

RR: 26/minPulse: 96/minTemp: 98.3 FBP: 116/70mm HgSPO2: 96%Weight: 25 kg (-1 to -2 SD)Height: 128 cms ( -1 to -2 SD )

Pallor +, Icterus +No clubbing/spider nevi/palmar erythemaPeriorbital puffiness +P/A: distended, soft Liver 2 cms BCM/span 10 cms, firm with sharp

margins Spleen 2 cms BCM, firm

FF+CVS – WNLChest – no added soundsCNS – WNL

Question?

Differential diagnosis?

Question?

How should this child be investigated further?

Investigations Investigations

Hb 8.3 Bil T/D 19.6/10.2TLC 13100 P32L63 AST/ALT 670/214Platelet count 113000 GGT 42

Peripheral smear

normocytes, few schistocytes Fragmented RBC’s

ALP 47

ESR 21 mm/hr Prot/Albumin 7.3/3.5

Retic count 7% (corrected) PT/INR 3.7

DCT negative BU/Cr 54/1.1

Urine R/M Positive for HbProtein 1 +

Uric acid 1.1LDH 886

Cultures sterile USG abdomen Coarse liver, spleen enlarged, mild ascites

Investigations

Anti-HAV IgM and total NR

HBsAg NR

Anti-HCV NR

Ceruloplasmin 8 mg/dl

24 Hr Urinary Copper (without challenge)

413 mcg/day

KF ring positive

ANA negative

Score 7 on WD criteria (Leipzig score) by Ferenci et al

Serum Cp <10 mg/dl +2Urine Cu > 2 ULN +2KF ring +2Coomb’s negative hemolytic anemia +1

Wilson's disease ( score > 4)

Acute Liver Failure in WD

Modest rises in serum aminotransferases (<< 2000 IU/L) Normal or markedly subnormal SAP AST/ALT >2.2 and ALP/Bil <4Coombs (–) hemolytic anemia and hemolysisRapid progression to renal failure

Korman J et al. Hepatology 2008Ferenci et al. Aliment Pharmacol Ther 2004 Roberts et al. AASLD. Hepatology 2008EASL. J Hepatol 2012

D3 of admissiondeveloped altered sensoriumdrowsyhyperreflexia

Question?

Is the diagnosis of Wilson’s disease confirmed?

Acute liver failure with grade 2 encephalopathy with coombs negative hemolysis with AKI

Wilson’s disease

Prognostication

ALF without encephalopathy

Modified Nazer scoreNew wilson’s index? PELD/MELD

Devarbhavi H et al. J Gastro Hepatol 2014

Nazer score

Nazer et al. Gut 1986

Score Bilirubinɥmol/L

INR ASTIU/L

WCCx 109/L

Albuming/L

0 0-100 0-1.29 0-100 0-6.7 >451 101-150 1.3-1.6 101-150 6.8-8.3 34-442 151-200 1.7-1.9 151-300 8.4-10.3 25-333 201-300 2.0-2.4 301-400 10.4-15.3 21-244 >301 >2.5 >401 >15.4 <20

Modified King’s score (New Wilson Index)

A score ≥ 11 urgent need for transplantationOur patient had a score of 16

Dhawan et al. Liver Transpl 2005

Multivariate analysis

Unadjusted hazard 95% Confidence P Ratio Interval Value

Enc 2.88 1.11 – 7.45 .03

T Bil 1.05 1.02 – 1.09 .002

Only encepaholopaty and total bilirubin emerged as independent predictors of mortality

Devarbhavi H. J Gastro Hepatol 2014

Score = 2.87 x encephalopathy + 1.07 x t bilirubin

ALF with encephalopathy

High mortality 80% (90% to 100% in some series)Liver transplantation is lifesaving

Berman et al. Gastroenterology 1991Roberts et al. AASLD. Hepatology 2008EASL. J Hepatol 2012Devarbhavi H et al. J Gastro Hepatol 2014

Question?

Treatment options in Wilsonian acute liver failure?

Child was taken for LRLT

Mother was donor

Question?

Donor evaluation/parents as donor in such cases

Sibling evaluation

First-degree relatives of any patient newly diagnosed with WD must be screened

Chance of a sibling being a homozygote and therefore developing clinical disease – is 25%

Analysis of the ATP7B gene for mutations in the children

Roberts et al. AASLD. Hepatology 2008EASL. J Hepatol 2012

POD # 1

post LT on POD#1 sensorium improved over the next 72 hours

Investigations

Hb 7.9

TLC 8100 P52L43

Platelet count 87000

Bil T/D 5.6/3.2AST/ALT 220/114ALP 83

Prot/Albumin 6.1/2.9

PT/INR 1.3

BU/Cr 21/0.6

POD#4

Child discharged on POD #19On tacrolimus, MMF and prednisoloneNo acute post-LT complicationsSteroids tapered and stopped by 3 months

Question?

Role of supportive therapy, plasmapheresis, hemodialysis and MARS

Neuro Wilson

Less common in children < 10 years old: neuro-psychiatric disorders 17%Average age of neurological dysfunction is 18.9 years In adults neurological dysfunction constitutes initial

clinical manifestation in 40–60%

Pfeiffer et al. Semin Neurol. 2007

LT in treatment of progressive neurological deterioration is controversial

Pfeiffer et al. Semin Neurol. 2007

Question

Role of LT in neuro Wilson?

Post LT outcome

Indication N/% Survival @1 year

5 year 10 year 15 year

EHBA 66.1% 91.3 89.5 86.9 84.8

ALF 72.6 69 67 67

WD: Japan 2.6% 98.3 96.5 94.4 73.4

UNOS 90 89

SPLIT 96 91.4

France 89% 87% 87% 87%

Arnon et al. Clin Transplant. 2011Kasahara et al. Am J of Transpl 2013Guillaud et al. J Hepatol. 2014

LT experiencePediatric 220

BA 81

Metabolic liver diseases 54

Cryptogenic 34

ALF 19

BCS 08

NNH 06

AIH 03

Hep B 03

Hyper oxaluria 02*

Poisoning 02

Hepatoblastoma 02

PVT 01**

Hep C 01

HCC 01

Chronic rejection 01

* combined LK** re transplant

Thank you!